Amyloid precursor protein-b facilitates cell adhesion during early development in zebrafish

Understanding the biological function of β-amyloid precursor protein (APP) beyond its role in Alzheimer9s disease is emerging. Yet, its function during embryonic development is poorly understood. The zebrafish APP homologue, Appb is strongly expressed during early development but has so far only been studied via morpholino-mediated knockdown. Zebrafish enables analysis of cellular processes in an ontogenic context, which is limited in many other vertebrates. We characterized zebrafish carrying a homozygous mutation that introduces a premature stop in exon 2 of the appb gene. We report that appb mutants are significantly smaller until 2dpf and display perturbed enveloping layer (EVL) integrity and cell protrusions at the blastula stage. Moreover, appb mutants surviving beyond 48 hpf exhibited no behavioral defects at 6 dpf and developed into healthy and fertile adults. The expression of app-family members, appa and aplp2, was found to be altered in mutants. Taken together, we show that appb orchestrates the initial development by supporting the integrity of the EVL, likely by mediating cell adhesion properties. The loss of Appb might be compensated for by other app family members to be able to implement continued normal development.